Isocardenolides

Zusammenfassung Ein einfacher Weg zur Synthese eines von zwei möglichen isomeren Cardenoliden wurde entwickelt und die Reaktionsfolge an Hand der Überführung von Pregnenolon in Isocardenolide V gezeigt.

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Steroids and Related Natural Products XXI. For the previous contribution refer to:G. R. Pettit andP. Hofer, Helv. chim. Acta46, 2142 (1963).

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A preliminary account of this study was presented (December 1963) at the VI. Pan-American Congress of Pharmacy and Biochemistry, Mexico City (Mexico).

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This investigation was supported by PHS Research Grants CY-4074 (C3) to CA-04074-06 from the National Cancer Institute, Public Health Service.     

An enhanced cosmic-ray flux towards zeta Persei inferred from a laboratory study of the H3+-e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many molecules. In dense interstellar clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density and temperature. But observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. Models of diffuse clouds have, however, been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons (e-), the electron fraction, and the cosmic-ray ionization rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards Persei) where the electron fraction is already known. From these, we find that the cosmic-ray ionization rate along this line of sight is 40 times faster than previously assumed. If such a high cosmic-ray flux is ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability

Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.